TY - JOUR
T1 - Longitudinal metabolomics in dried bloodspots yields profiles informing newborn screening for succinic semialdehyde dehydrogenase deficiency
AU - Brown, Madalyn
AU - Turgeon, Coleman
AU - Rinaldo, Piero
AU - Pop, Ana
AU - Salomons, Gajja S.
AU - Roullet, Jean Baptiste
AU - Michael Gibson, K.
PY - 2020/5
Y1 - 2020/5
N2 - Analyses of 19 amino acids, 38 acylcarnitines, and 3 creatine analogues (https://clir.mayo.edu) were implemented to test the hypothesis that succinic semialdehyde dehydrogenase deficiency (SSADHD) could be identified in dried bloodspots (DBS) using currently available newborn screening methodology. The study population included 17 post-newborn SSADHD DBS (age range 0.8-38 years; median, 8.2 years; 10 M; controls, 129-353 age-matched individuals, mixed gender) and 10 newborn SSADHD DBS (including first and second screens from 3 of 7 patients). Low (informative) markers in post-newborn DBS included C2- and C4-OH carnitines, ornithine, histidine and creatine, with no gender differences. For newborn DBS, informative markers included C2-, C3-, C4- and C4-OH carnitines, creatine and ornithine. Of these, only creatine demonstrated a significant change with age, revealing an approximate 4-fold decrease. We conclude that quantitation of short-chain acylcarnitines, creatine, and ornithine provides a newborn DBS profile with potential as a first tier screening tool for early detection of SSADHD. This first tier evaluation can be readily verified using a previously described second tier liquid chromatography-tandem mass spectrometry method for γ-hydroxybutyric acid in the same DBS. More extensive evaluation of this first/second tier screening approach is needed in a larger population.
AB - Analyses of 19 amino acids, 38 acylcarnitines, and 3 creatine analogues (https://clir.mayo.edu) were implemented to test the hypothesis that succinic semialdehyde dehydrogenase deficiency (SSADHD) could be identified in dried bloodspots (DBS) using currently available newborn screening methodology. The study population included 17 post-newborn SSADHD DBS (age range 0.8-38 years; median, 8.2 years; 10 M; controls, 129-353 age-matched individuals, mixed gender) and 10 newborn SSADHD DBS (including first and second screens from 3 of 7 patients). Low (informative) markers in post-newborn DBS included C2- and C4-OH carnitines, ornithine, histidine and creatine, with no gender differences. For newborn DBS, informative markers included C2-, C3-, C4- and C4-OH carnitines, creatine and ornithine. Of these, only creatine demonstrated a significant change with age, revealing an approximate 4-fold decrease. We conclude that quantitation of short-chain acylcarnitines, creatine, and ornithine provides a newborn DBS profile with potential as a first tier screening tool for early detection of SSADHD. This first tier evaluation can be readily verified using a previously described second tier liquid chromatography-tandem mass spectrometry method for γ-hydroxybutyric acid in the same DBS. More extensive evaluation of this first/second tier screening approach is needed in a larger population.
KW - Acylcarnitines
KW - Amino acids
KW - Creatine
KW - Dried bloodspots
KW - Newborn screening
KW - Succinic semialdehyde dehydrogenase deficiency
UR - http://www.scopus.com/inward/record.url?scp=85085122572&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/jmd2.12075
DO - https://doi.org/10.1002/jmd2.12075
M3 - Article
C2 - 32395407
SN - 2192-8304
VL - 53
SP - 29
EP - 38
JO - JIMD reports
JF - JIMD reports
IS - 1
ER -